Acalabrutinib for Waldenström Macroglobulinemia

Recruiting at 37 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Acerta Pharma BV

Must not be taking: BCR inhibitors, BCL-2 inhibitors, Anticoagulants, PPIs

Disqualifiers: Prior malignancy, Cardiovascular disease, Autoimmune anemia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 28

Duration: Up to approximately 3.8 years

107 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the safety, pharmacokinetics, pharmacodynamics, and activity of acalabrutinib in treating subjects with WM.

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but you cannot take certain medications like immunotherapy within 4 weeks of starting, or anticoagulants like warfarin within 28 days of starting. You also cannot use proton-pump inhibitors during the trial.

How is the drug Acalabrutinib different from other treatments for Waldenström Macroglobulinemia?

Acalabrutinib is a newer, more selective Bruton tyrosine kinase (BTK) inhibitor compared to older treatments like ibrutinib, which means it targets the cancer cells more precisely and may have fewer side effects. It is used as a monotherapy, meaning it is given alone without combining with other drugs, which can reduce the risk of toxic effects seen with traditional chemoimmunotherapy. ^{1 2 3 4 5}

Research Team

AstraZeneca Clinical study Information Center

Principal Investigator

1-877-240-9479 [e-mail]

Eligibility Criteria

This trial is for adults with Waldenström Macroglobulinemia (WM), a type of blood cancer. It's open to those who haven't been treated before and want an alternative to chemoimmunotherapy, as well as patients whose WM has returned or didn't respond to at least one prior treatment. Participants must be able to swallow capsules and agree to use effective contraception if applicable.

Inclusion Criteria

I can swallow capsules without difficulty and can participate in all study procedures.

Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (in accordance with national and local patient privacy regulations)

I agree to use effective birth control during and 2 days after the study.

Exclusion Criteria

I do not have serious heart problems like recent heart attacks or severe heart failure.

I haven't had immunotherapy in the last 4 weeks.

I had cancer before, but it was either skin cancer treated successfully, cervical cancer that did not spread, or another type from which I've been free for 2+ years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive acalabrutinib to evaluate safety, pharmacokinetics, pharmacodynamics, and activity in treating Waldenström Macroglobulinemia

Up to approximately 3.8 years

Cycle-based visits every 28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Acalabrutinib (ACP-196)

Trial Overview The study is testing Acalabrutinib (ACP-196) for safety and effectiveness in treating WM. Researchers will look at how the body processes the drug, its impact on the disease, and any potential benefits it may offer.

Participant Groups

Group I: Treatment Naïve Experimental Treatment 1 Intervention

Subjects with treatment-naïve Waldenström Macroglobulinemia. N=14

Group II: Previously Treated Experimental Treatment 1 Intervention

Subjects previously treated with Waldenström Macroglobulinemia N=92

Who Is Running the Clinical Trial?

Acerta Pharma BV

Lead Sponsor

Trials

46

Recruited

5,900+

Findings from Research

Acalabrutinib, a second-generation BTK inhibitor, has been shown to be more potent and selective than the first-in-class BTK inhibitor, ibrutinib, in treating B cell malignancies.

The review highlights the growing availability of targeted therapies for B cell cancers, emphasizing the potential of acalabrutinib based on preclinical and clinical data.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acalabrutinib (ACP-196): a selective second-generation BTK inhibitor. Wu, J., Zhang, M., Liu, D.[2018]

In a phase II study of tirabrutinib for Waldenström's macroglobulinemia involving 27 patients, 93% showed a major response, with high progression-free (92.6%) and overall survival (100%) rates at 24 months, indicating strong efficacy.

The treatment was generally well-tolerated, with manageable side effects; however, some patients experienced grade 3-4 neutropenia and other adverse events, suggesting that while effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two-year outcomes of tirabrutinib monotherapy in Waldenström's macroglobulinemia. Sekiguchi, N., Rai, S., Munakata, W., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Acalabrutinib monotherapy in patients with Waldenström macroglobulinemia: a single-arm, multicentre, phase 2 study. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Acalabrutinib (ACP-196): a selective second-generation BTK inhibitor. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Zanubrutinib for the treatment of patients with Waldenström macroglobulinemia: 3 years of follow-up. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Zanubrutinib for the treatment of MYD88 wild-type Waldenström macroglobulinemia: a substudy of the phase 3 ASPEN trial. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Two-year outcomes of tirabrutinib monotherapy in Waldenström's macroglobulinemia. [2022]